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A 6-mRNA host response classifier in whole blood predicts outcomes in COVID-19 and other acute viral infections.
Buturovic, Ljubomir; Zheng, Hong; Tang, Benjamin; Lai, Kevin; Kuan, Win Sen; Gillett, Mark; Santram, Rahul; Shojaei, Maryam; Almansa, Raquel; Nieto, Jose Ángel; Muñoz, Sonsoles; Herrero, Carmen; Antonakos, Nikolaos; Koufargyris, Panayiotis; Kontogiorgi, Marina; Damoraki, Georgia; Liesenfeld, Oliver; Wacker, James; Midic, Uros; Luethy, Roland; Rawling, David; Remmel, Melissa; Coyle, Sabrina; Liu, Yiran E; Rao, Aditya M; Dermadi, Denis; Toh, Jiaying; Jones, Lara Murphy; Donato, Michele; Khatri, Purvesh; Giamarellos-Bourboulis, Evangelos J; Sweeney, Timothy E.
  • Buturovic L; Inflammatix, Inc., 863 Mitten Rd, Suite 104, Burlingame, CA, 94010, USA.
  • Zheng H; Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Palo Alto, CA, 94305, USA.
  • Tang B; Center for Biomedical Informatics Research, Department of Medicine, Stanford University, Stanford, CA, 94305, USA.
  • Lai K; Centre for Immunology and Allergy Research, Westmead Institute for Medical Research, Sydney, Australia.
  • Kuan WS; Department of Intensive Care Medicine, Nepean Hospital, Sydney, Australia.
  • Gillett M; Nepean Genomic Research Group, Nepean Clinical School, University of Sydney, Sydney, Australia.
  • Santram R; Marie Bashir Institute for Infectious Diseases and Biosecurity, Sydney, Australia.
  • Shojaei M; Department of Emergency Medicine, Westmead Hospital, Sydney, Australia.
  • Almansa R; Department of Emergency Medicine, National University Hospital Singapore, Singapore, Singapore.
  • Nieto JÁ; Department of Emergency Medicine, Royal North Shore Hospital, Sydney, Australia.
  • Muñoz S; Department of Emergency Medicine, St Vincent Hospital, Sydney, Australia.
  • Herrero C; Centre for Immunology and Allergy Research, Westmead Institute for Medical Research, Sydney, Australia.
  • Antonakos N; Department of Intensive Care Medicine, Nepean Hospital, Sydney, Australia.
  • Koufargyris P; Group for Biomedical Research in Sepsis (BioSepsis), Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.
  • Kontogiorgi M; Hospital Universitario Río Hortega, Valladolid, Spain.
  • Damoraki G; Servicio de Urgencias de Atención Primaria, Salamanca, Spain.
  • Liesenfeld O; Servicio de Urgencias de Atención Primaria, Salamanca, Spain.
  • Wacker J; Servicio de Urgencias de Atención Primaria, Salamanca, Spain.
  • Midic U; 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, 124 62, Athens, Greece.
  • Luethy R; 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, 124 62, Athens, Greece.
  • Rawling D; 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, 124 62, Athens, Greece.
  • Remmel M; 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, 124 62, Athens, Greece.
  • Coyle S; Inflammatix, Inc., 863 Mitten Rd, Suite 104, Burlingame, CA, 94010, USA.
  • Liu YE; Inflammatix, Inc., 863 Mitten Rd, Suite 104, Burlingame, CA, 94010, USA.
  • Rao AM; Inflammatix, Inc., 863 Mitten Rd, Suite 104, Burlingame, CA, 94010, USA.
  • Dermadi D; Inflammatix, Inc., 863 Mitten Rd, Suite 104, Burlingame, CA, 94010, USA.
  • Toh J; Inflammatix, Inc., 863 Mitten Rd, Suite 104, Burlingame, CA, 94010, USA.
  • Jones LM; Inflammatix, Inc., 863 Mitten Rd, Suite 104, Burlingame, CA, 94010, USA.
  • Donato M; Inflammatix, Inc., 863 Mitten Rd, Suite 104, Burlingame, CA, 94010, USA.
  • Khatri P; Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Palo Alto, CA, 94305, USA.
  • Giamarellos-Bourboulis EJ; Cancer Biology Program, Stanford University, Stanford, CA, 94305, USA.
  • Sweeney TE; Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Palo Alto, CA, 94305, USA.
Sci Rep ; 12(1): 889, 2022 01 18.
Article in English | MEDLINE | ID: covidwho-1630723
ABSTRACT
Predicting the severity of COVID-19 remains an unmet medical need. Our objective was to develop a blood-based host-gene-expression classifier for the severity of viral infections and validate it in independent data, including COVID-19. We developed a logistic regression-based classifier for the severity of viral infections and validated it in multiple viral infection settings including COVID-19. We used training data (N = 705) from 21 retrospective transcriptomic clinical studies of influenza and other viral illnesses looking at a preselected panel of host immune response messenger RNAs. We selected 6 host RNAs and trained logistic regression classifier with a cross-validation area under curve of 0.90 for predicting 30-day mortality in viral illnesses. Next, in 1417 samples across 21 independent retrospective cohorts the locked 6-RNA classifier had an area under curve of 0.94 for discriminating patients with severe vs. non-severe infection. Next, in independent cohorts of prospectively (N = 97) and retrospectively (N = 100) enrolled patients with confirmed COVID-19, the classifier had an area under curve of 0.89 and 0.87, respectively, for identifying patients with severe respiratory failure or 30-day mortality. Finally, we developed a loop-mediated isothermal gene expression assay for the 6-messenger-RNA panel to facilitate implementation as a rapid assay. With further study, the classifier could assist in the risk assessment of COVID-19 and other acute viral infections patients to determine severity and level of care, thereby improving patient management and reducing healthcare burden.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: RNA, Messenger / Gene Expression Regulation / SARS-CoV-2 / COVID-19 Type of study: Controlled clinical trial / Observational study / Prognostic study / Randomized controlled trials / Risk factors Limits: Female / Humans / Male / Middle aged Language: English Journal: Sci Rep Year: 2022 Document Type: Article Affiliation country: S41598-021-04509-9

Full text: Available Collection: International databases Database: MEDLINE Main subject: RNA, Messenger / Gene Expression Regulation / SARS-CoV-2 / COVID-19 Type of study: Controlled clinical trial / Observational study / Prognostic study / Randomized controlled trials / Risk factors Limits: Female / Humans / Male / Middle aged Language: English Journal: Sci Rep Year: 2022 Document Type: Article Affiliation country: S41598-021-04509-9